Germicidal method for eradicating or preventing the formation of biofilms

ABSTRACT

A method of treatment for a tissue organ or entire body of a patient prior to or after exposure to a biofilm infection comprises the steps of activating an acoustic shock wave generator or source to emit acoustic shock waves; and subjecting the infected tissue, organ or entire body to the acoustic shock waves stimulating said tissue, organ or body wherein the tissue, organ or body is positioned within a path of the emitted shock waves.

RELATED APPLICATIONS

This application is a continuation in part of U.S. patent applicationSer. No. 11/122,154 filed on May 4, 2005 now U.S. Pat. No. 7,470,240entitled “Pressure Pulse/Shock Wave Therapy Methods and an Apparatus forConducting the Therapeutic Methods” and U.S. patent application Ser. No.11/071,156 filed on Mar. 4, 2005 entitled “Pressure Pulse/Shock WaveApparatus for Generating Waves Having Nearly Plane or DivergentCharacteristics” and also claims benefit of priority to U.S. ProvisionalPatent Application Ser. No. 60/693,369 filed Jun. 22, 2005; U.S.Provisional Patent Application Ser. No. 60/693,143 filed Jun. 23, 2005;U.S. Provisional Patent Application Ser. No. 60/621,028 filed Oct. 22,2004 and of U.S. Provisional Patent Application Ser. No. 60/642,149filed Jan. 10, 2005, the disclosures of which are incorporated herein byreference in their entirety.

FIELD OF THE INVENTION

The present invention relates to germicidal methods to eradicateformations of biofilms and to methods to prevent the formation of suchbiofilms.

BACKGROUND OF THE INVENTION

Almost all living creatures including plants are formed of cellulartissues. In virtually every living being these cellular communities forman outer protective barrier of tissues. In mammals this protectivebarrier is commonly referred to as skin. Similarly in vegetables andplants the outer shell is really a protective barrier of skin or a peelthat grows as the vegetable or fruit matures providing a shield fromintrusions to the underlying and generally more vulnerable inner tissue.For example in citrus fruits the juicy high liquid content of thesetissues would be impossible to mature without the protective outer peel.

Accordingly the use of such natural shields or barriers to protect morevulnerable cells or tissue is the norm.

It is therefore of little surprise that on the molecular level bacteriawhether aerobic or anaerobic have generally been known to exhibit anouter protective cellular membrane similar to a skin and any treatmentto destroy such a bacteria typically required weakening or penetratingthis outer membrane. Once penetration occurred the viability of theorganism was diminished resulting in a cessation of viability.

Bacteria while being a relatively lower order entity has nonetheless avery strong and evolutionary desire to survive and thus is one of themore adaptive organisms found on earth. Mutant strains of bacteria arecommonly feared because of their huge capacity to adapt to threatsparticularly those involving the use of microbial disinfectants andantibiotics used to fight disease.

Microorganisms grow through a form of cellular division. Blood agarcultures are used to grow colonies of bacteria. The cluster starts outinvisible to the naked eye and within 24 to 48 hours can be a largecolony of millions of bacteria. This has always been a well knownphenomenon of bacterial growth.

Now, however, this colony building technique has been adapted to formmulti-layered barrier structures and shields similar to a skin. Thisprotective barrier building is now referred to as biofilms.

In U.S. Pat. No. 6,726,898 entitled “Local delivery of agents fordisruption and inhibition of bacterial biofilm for treatment ofperiodontal disease” the inventors refer to the work of J. W. Costertonet al, Microbial biofilms, Annu. Rev. Microbial 49:711 (1995) whereinthey recite:

-   -   Recent attention has been given to removing unwanted biofilms        forming in various industrial processes. Biofilms are        notoriously resistant to removal. The tendency of bacteria to        adhere, secrete an adhesive extra cellular matrix and grow is a        strong evolutionary advantage difficult to overcome. So far,        little success has been realized. Observation of living        bacterial biofilms by modern methods has established that these        microbial populations form a very complicated structural        architecture. See, e.g., J. W. Costerton, et al., Microbial        biofilms, Annu. Rev. Microbial, 49:711 (1995). This suggested        the operation of a cell—cell signaling mechanism for bacteria to        produce these complex structures. After twenty years of        research, it is generally assumed now that all enteric bacteria        and gram negative bacteria are capable of cell density        regulation using acylated homoserine lactones (AHLs) as        autoinducer molecules.    -   In early stages a biofilm is comprised of a cell layer attached        to a surface. The cells grow and divide, forming a dense mat        numerous layers thick. When sufficient numbers of bacteria are        present (quorum) they signal each other to reorganize forming an        array of pillars and irregular surface structures, all connected        by convoluted channels that deliver food and remove waste. The        biofilm produces a glycocalyx matrix shielding them from the        environment. Urinary tract and urinary catheter infections are        examples of biofilm infections.    -   As the biofilm matures, the bacteria become greatly more        resistant to antibiotics than when in the planktonic (free cell)        state. See H. Anwar, et al, Establishment of aging biofilms: a        possible mechanism of bacterial resistance to antimicrobial        therapy, Antimicrob Agents Chemother 36:1347 (1992). The host        immune system is also significantly less effective against        bacteria in the biofilm state. See E. T. Jensen, et al, Human        polymorphonuclear leukocyte response to Pseudomonas aeruginosa        biofilms, Infect Immun 5:2383 (1990). Certain bacterial strains        may be able to confer resistance protecting the biofilm from        host defense components that would otherwise bind to the surface        of viable bacteria and kill them.

In U.S. Pat. No. 6,777,223 entitled “Methods for eliminating theformation of biofilm”, the inventors describe biofilms as:

-   -   biological films that develop and persist at the surfaces of        biotic or abiotic objects in aqueous environments from the        adsorption of microbial cells onto the solid surfaces. This        adsorption can provide a competitive advantage for the        microorganisms since they can reproduce, are accessible to a        wider variety of nutrients and oxygen conditions, are not washed        away, and are less sensitive to antimicrobial agents. The        formation of the biofilm is also accompanied by the production        of exo-polymeric materials (polysaccharides, polyuronic acids,        alginates, glycoproteins, and proteins) which together with the        cells form thick layers of differentiated structures separated        by water-filled spaces. The resident microorganisms may be        individual species of microbial cells or mixed communities of        microbial cells, which may include aerobic and anaerobic        bacteria, algae, protozoa, and fungi. Thus, the biofilm is a        complex assembly of living microorganisms embedded in an organic        structure composed of one or more matrix polymers which are        secreted by the resident microorganisms.

This prior art invention related to methods for preventing or removingbiofilm on a surface, comprising contacting the surface with aneffective amount of a composition comprising one or more acylases and acarrier to degrade a lactone produced by one or more microorganisms,wherein the degradation of the lactone prevents or removes the biofilm.

Similarly U.S. Pat. No. 6,875,422 suggests the use of one or more of anoral bacterial flora controlling agent as a treatment for biofilms foundin the periodontal pocket.

Almost all of the prior art literature on the subject of eliminating orpreventing biofilms suggests one or more drugs or chemical agents as thesolution to this problem as well as well known cleaning procedures suchas debridement in the practice of periodontal treatments.

What is sorely lacking is a safe and reliable method to break down thecellular barrier properties of these complex architectural microbialstructures called biofilms.

It is therefore an object of the present invention to provide such amethod to reduce or eradicate microbial biofilms not only on surfaces,but within tissues and organs.

SUMMARY OF THE INVENTION

The present invention uses pressure pulse or acoustic shock waves as ameans to attack and penetrate through the barrier shield architecture ofa mass of biofilm to destroy the microbial colony residing under andwithin the biofilms protective layer.

The present invention provides a means for fracturing and breaking theouter biofilms barrier into fragments that can be absorbed or flushedaway by healthy cells of the host as well as exposing the colony ofmicroorganisms within the biofilms for eradication.

The present invention provides a germicidal energy that alone or incombination with stimulated healthy cells of the host destroys thecolony and its ability to manufacture a biofilm barrier.

The present invention can be used in combination with surgicalprocedures or with drugs or antibiotics or other forms of medicaments toeradicate the biofilms mass.

In one embodiment of the invention the present method is used as apre-occurrence preventative treatment prior to the formation of abiomass for patients of high risk for the occurrence.

In other embodiments the method is used post-occurrence for thetreatment of biofilms found in or on tissues or organs such as theurinary tract, the reproductive organs, the heart, more particularlyheart valves with deposits of one or more biofilms.

As used throughout the invention the host is considered to be anybiofilm supporting system or being. In mammals the being may be ananimal or a human. The system may be any system be it mechanical orliving. In living systems, it may be the cardiovascular system, theurological or the reproductive system, the digestive system, theneurological, the periodontal region of teeth and gums or any tissue ororgan found in the host of a biofilm or at risk or candidate host.

Definitions

“aerobic” living, active, or occurring only in the presence of oxygen.

“anaerobic” living, active, or occurring in the absence of free oxygen.

“apoptosis” is the biological process of controlled, programmed celldeath, by means of which cells die by a process of condensation withoutthe release of cell contents into the surrounding milieu.

A “curved emitter” is an emitter having a curved reflecting (orfocusing) or emitting surface and includes, but is not limited to,emitters having ellipsoidal, parabolic, quasi parabolic (generalparaboloid) or spherical reflector/reflecting or emitting elements.Curved emitters having a curved reflecting or focusing element generallyproduce waves having focused wave fronts, while curved emitters having acurved emitting surfaces generally produce wave having divergent wavefronts.

“cystic fibrosis” a common disease especially in Caucasian populationsthat appears usually in early childhood, is inherited as a recessivemonogenic trait, involves functional disorder of the exocrine glands,and is marked especially by faulty digestion due to a deficiency ofpancreatic enzymes, by difficulty in breathing due to mucus accumulationin airways, and by excessive loss of salt in the sweat.

“cytoplasm” The part of a cell that contains the CYTOSOL and smallstructures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES.

“Divergent waves” in the context of the present invention are all waveswhich are not focused and are not plane or nearly plane. Divergent wavesalso include waves which only seem to have a focus or source from whichthe waves are transmitted. The wave fronts of divergent waves havedivergent characteristics. Divergent waves can be created in manydifferent ways, for example: A focused wave will become divergent onceit has passed through the focal point. Spherical waves are also includedin this definition of divergent waves and have wave fronts withdivergent characteristics.

“endocarditis” inflammation of the lining of the heart and its valves.

“extracorporeal” occurring or based outside the living body.

A “generalized paraboloid” according to the present invention is also athree-dimensional bowl. In two dimensions (in Cartesian coordinates, xand y) the formula y^(n)=2px [with n being ≠2, but being greater thanabout 1.2 and smaller than 2, or greater than 2 but smaller than about2.8]. In a generalized paraboloid, the characteristics of the wavefronts created by electrodes located within the generalized paraboloidmay be corrected by the selection of (p (−z, +z)), with z being ameasure for the burn down of an electrode, and n, so that phenomenaincluding, but not limited to, burn down of the tip of an electrode (−z,+z) and/or disturbances caused by diffraction at the aperture of theparaboloid are compensated for.

“lactate dehydrogenase (LDH)” A tetrameric enzyme that, along with thecoenzyme NAD+, catalyzes the interconversion of lactate and pyruvate. Invertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C)exist.

“mitochondria” Semiautonomous, self-reproducing organelles that occur inthe cytoplasm of all cells of most, but not all, eukaryotes. Eachmitochondrion is surrounded by a double limiting membrane. The innermembrane is highly invaginated, and its projections are called cristae.Mitochondria are the sites of the reactions of oxidativephosphorylation, which result in the formation of ATP. They containdistinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNASYNTHETASES; and elongation and termination factors. Mitochondria dependupon genes within the nucleus of the cells in which they reside for manyessential messenger RNAs (RNA, MESSENGER). Mitochondria are believed tohave arisen from aerobic bacteria that established a symbioticrelationship with primitive protoeukaryotes.

“necrosis” A pathological process caused by the progressive degradativeaction of enzymes that is generally associated with severe cellulartrauma. It is characterized by mitochondrial swelling, nuclearflocculation, uncontrolled cell lysis, and ultimately CELL DEATH.

A “paraboloid” according to the present invention is a three-dimensionalreflecting bowl. In two dimensions (in Cartesian coordinates, x and y)the formula y²=2px, wherein p/2 is the distance of the focal point ofthe paraboloid from its apex, defines the paraboloid. Rotation of thetwo-dimensional figure defined by this formula around its longitudinalaxis generates a de facto paraboloid.

“phagocytosis” The engulfing of microorganisms, other cells, and foreignparticles by phagocytic cells.

“Plane waves” are sometimes also called flat or even waves. Their wavefronts have plane characteristics (also called even or parallelcharacteristics). The amplitude in a wave front is constant and the“curvature” is flat (that is why these waves are sometimes called flatwaves). Plane waves do not have a focus to which their fronts move(focused) or from which the fronts are emitted (divergent). “Nearlyplane waves” also do not have a focus to which their fronts move(focused) or from which the fronts are emitted (divergent). Theamplitude of their wave fronts (having “nearly plane” characteristics)is approximating the constancy of plain waves. “Nearly plane” waves canbe emitted by generators having pressure pulse/shock wave generatingelements with flat emitters or curved emitters. Curved emitters maycomprise a generalized paraboloid that allows waves having nearly planecharacteristics to be emitted.

A “pressure pulse” according to the present invention is an acousticpulse which includes several cycles of positive and negative pressure.The amplitude of the positive part of such a cycle should be above about0.1 MPa and its time duration is from below a microsecond to about asecond. Rise times of the positive part of the first pressure cycle maybe in the range of nano-seconds (ns) up to some milli-seconds (ms). Veryfast pressure pulses are called shock waves. Shock waves used in medicalapplications do have amplitudes above 0.1 MPa and rise times of theamplitude are below 100's of ns. The duration of a shock wave istypically below 1-3 micro-seconds (μs)for the positive part of a cycleand typically above some micro-seconds for the negative part of a cycle.

Waves/wave fronts described as being “focused” or “having focusingcharacteristics” means in the context of the present invention that therespective waves or wave fronts are traveling and increase theiramplitude in direction of the focal point. Per definition the energy ofthe wave will be at a maximum in the focal point or, if there is a focalshift in this point, the energy is at a maximum near the geometricalfocal point. Both the maximum energy and the maximal pressure amplitudemay be used to define the focal point.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be described by way of example and with reference tothe accompanying drawings in which:

FIG. 1 a is a simplified depiction of a pressure pulse/shock wave(PP/SW) generator with focusing wave characteristics.

FIG. 1 b is a simplified depiction of a pressure pulse/shock wavegenerator with plane wave characteristics.

FIG. 1 c is a simplified depiction of a pressure pulse/shock wavegenerator with divergent wave characteristics.

FIG. 2 a is a simplified depiction of a pressure pulse/shock wavegenerator having an adjustable exit window along the pressure wave path.The exit window is shown in a focusing position.

FIG. 2 b is a simplified depiction of a pressure pulse/shock wavegenerator having an exit window along the pressure wave path. The exitwindow as shown is positioned at the highest energy divergent position.

FIG. 2 c is a simplified depiction of a pressure pulse/shock wavegenerator having an exit window along the pressure wave path. The exitwindow is shown at a low energy divergent position.

FIG. 3 is a simplified depiction of an electro-hydraulic pressurepulse/shock wave generator having no reflector or focusing element.Thus, the waves of the generator did not pass through a focusing elementprior to exiting it.

FIG. 4 a is a simplified depiction of a pressure pulse/shock wavegenerator having a focusing element in the form of an ellipsoid. Thewaves generated are focused.

FIG. 4 b is a simplified depiction of a pressure pulse/shock wavegenerator having a parabolic reflector element and generating waves thatare disturbed plane.

FIG. 4 c is a simplified depiction of a pressure pulse/shock wavegenerator having a quasi parabolic reflector element (generalizedparaboloid) and generating waves that are nearly plane/have nearly planecharacteristics.

FIG. 4 d is a simplified depiction of a generalized paraboloid withbetter focusing characteristic than a paraboloid in which n=2. Theelectrode usage is shown. The generalized paraboloid, which is aninterpolation (optimization) between two optimized paraboloids for a newelectrode and for a used (burned down) electrode is also shown.

FIG. 5 is a simplified depiction of a pressure pulse/shock wavegenerator being connected to a control/power supply unit.

FIG. 6 is a simplified depiction of a pressure pulse/shock wavegenerator comprising a flat EMSE (electromagnetic shock wave emitter)coil system to generate nearly plane waves as well as an acoustic lens.Convergent wave fronts are leaving the housing via an exit window.

FIG. 7 is a simplified depiction of a pressure pulse/shock wavegenerator having a flat EMSE coil system to generate nearly plane waves.The generator has no reflecting or focusing element. As a result, thepressure pulse/shock waves are leaving the housing via the exit windowunfocused having nearly plane wave characteristics.

FIG. 8 is a simplified depiction of a pressure pulse/shock wavegenerator having a flat piezoceramic plate equipped with a single ornumerous individual piezoceramic elements to generate plane waveswithout a reflecting or focusing element. As a result, the pressurepulse/shock waves are leaving the housing via the exit window unfocusedhaving nearly plane wave characteristics.

FIG. 9 is a simplified depiction of a pressure pulse/shock wavegenerator having a cylindrical EMSE system and a triangular shapedreflecting element to generate plane waves. As a result, the pressurepulse/shock waves are leaving the housing via the exit window unfocusedhaving nearly plane wave characteristics.

FIG. 10 is a simplified depiction of a pressure pulse/shock wave (PP/SW)generator with focusing wave characteristics shown focused with thefocal point or geometrical focal volume being on an organ, the focusbeing targeted on the location X₀.

FIG. 11 is a simplified depiction of a pressure pulse/shock wave (PP/SW)generator with the focusing wave characteristics shown wherein the focusis located a distance X, from the location X₀ of an organ wherein theconverging waves impinge the organ.

FIG. 12 is a simplified depiction of a pressure pulse/shock wave (PP/SW)generator with focusing wave characteristics shown wherein the focus islocated a distance X₂ from the mass location X₀ wherein the emitteddivergent waves impinge the organ.

DETAILED DESCRIPTION OF THE INVENTION

In the pressure pulse or shock wave method of treating a tissue, anorgan or the entire body of a host be it mechanical system or a mammal,the host system or mammal be it human or an animal with a risk ofexposure to a biofilm or post-occurrence of such biofilms requires thehost patient to be positioned in a convenient orientation to permit thesource of the emitted waves to most directly send the waves to thetarget site to initiate pressure pulse or shock wave stimulation of thetarget area with minimal, preferably no obstructing features in the pathof the emitting source or lens. Assuming the biofilm target area or siteis within a projected area of the wave transmission, a singletransmission dosage of wave energy may be used. The transmission dosagecan be from a few seconds to 20 minutes or more dependent on thecondition. Preferably the waves are generated from an unfocused orfocused source. The unfocused waves can be divergent, planar or nearplanar and having a low pressure amplitude and density in the range of0.00001 mJ/mm² to 1.0 mJ/mm² or less, most typically below 0.2 mJ/mm².The focused source preferably can use a diffusing lens or have afar-sight focus to minimize if not eliminate having the localized focuspoint within the tissue. Preferably the focused shock waves are used ata similarly effective low energy transmission or alternatively can be athigher energy but wherein the tissue target site is disposedpre-convergence inward of the geometric focal point of the emitted wavetransmission. In treating some hard to penetrate biofilms, the pressurepulse more preferably is a high energy target focused wave pattern whichcan effectively attack the biofilm outer structure or barrier shieldcausing fractures or openings to be created to expose the colonies ofmicroorganisms within the biofilm to the germicidal effects of thepressure pulses or shock waves. This emitted energy destroys theunderlying microorganism's cellular membranes. In addition thefragmentation of the biofilms outer barrier is then easily absorbed byor flushed out of the host. The surrounding healthy cells in the regiontreated are activated initiating a defense mechanism response to assistin eradication of the unwanted infection.

These shock wave energy transmissions are effective in stimulating acellular response and can be accomplished without creating thecavitation bubbles in the tissue of the target site when employed inother than high energy focused transmissions. This effectively insuresthe tissue or organ does not have to experience the sensation ofhemorrhaging so common in the higher energy focused wave forms having afocal point at or within the targeted treatment site.

If the target site is an organ subjected to a surgical procedureexposing at least some if not all of the organ within the body cavitythe target site may be such that the patient or the generating sourcemust be reoriented relative to the site and a second, third or moretreatment dosage can be administered. The fact that some if not all ofthe dosage can be at a low energy the common problem of localizedhemorrhaging is reduced making it more practical to administer multipledosages of waves from various orientations to further optimize thetreatment and cellular stimulation of the target site. Heretoforefocused high energy multiple treatments induced pain and discomfort tothe patient. The use of low energy focused or un-focused waves at thetarget site enables multiple sequential treatments.

The present method may need precise site location and can be used incombination with such known devices as ultrasound, cat-scan or x-rayimaging if needed. The physician's general understanding of the anatomyof the patient may be sufficient to locate the target area to betreated. This is particularly true when the exposed tissue or portion ofthe infected body or organ is visually within the surgeon's line ofsight and this permits the lens or cover of the emitting shock wavesource to impinge on the affected organ or tissue directly or through atransmission enhancing gel, water or fluid medium during the pressurepulse or shock wave treatment. The treated area can withstand a fargreater number of shock waves based on the selected energy level beingemitted. For example at very low energy levels the stimulation exposurecan be provided over prolonged periods as much as 20 minutes if sodesired. At higher energy levels the treatment duration can be shortenedto less than a minute, less than a second if so desired. The limitingfactor in the selected treatment dosage is avoidance or minimization ofsurrounding cell hemorrhaging and other kinds of damage to thesurrounding cells or tissue while still providing a stimulating stemcell activation or a cellular release or activation of VEGF and othergrowth factors while simultaneously germicidally attacking the biofilmbarrier and underlying colony of microorganisms.

Due to the wide range of beneficial treatments available it is believedpreferable that the optimal use of one or more wave generators orsources should be selected on the basis of the specific application.Wherein relatively small target sites may involve a single wavegenerator placed on an adjustable manipulator arm. A key advantage ofthe present inventive methodology is that it is complimentary toconventional medical procedures. In the case of any operative surgicalprocedure the surgical area of the patient can be bombarded with theseenergy waves to stimulate cellular release of healing agents and growthfactors. This will dramatically reduce the healing process time. Mostpreferably such patients may be provided more than one such treatmentwith an intervening dwell time for cellular relaxation prior tosecondary and tertiary post operative treatments.

The underlying principle of these pressure pulse or shock wave therapymethods is to attack the biofilm directly and to stimulate the body'sown natural healing capability. This is accomplished by deploying shockwaves to stimulate strong cells in the surrounding tissue to activate avariety of responses. The acoustic shock waves transmit or trigger whatappears to be a cellular communication throughout the entire anatomicalstructure, this activates a generalized cellular response at thetreatment site, in particular, but more interestingly a systemicresponse in areas more removed from the wave form pattern. This isbelieved to be one of the reasons molecular stimulation can be conductedat threshold energies heretofore believed to be well below thosecommonly accepted as required. Accordingly not only can the energyintensity be reduced in some cases, but also the number of applied shockwave impulses can be lowered from several thousand to as few as one ormore pulses and still yield a beneficial stimulating response. The keyis to provide at least a sufficient amount of energy to weaken thebiofilms protective outer barrier or shield. This weakening can beachieved by any fracture or opening that exposes the underlying colonyof microorganisms.

The use of shock waves as described above appears to involve factorssuch as thermal heating, light emission, electromagnetic field exposure,chemical releases in the cells as well as a microbiological responsewithin the cells. Which combination of these factors plays a role instimulating healing is not yet resolved. However, there appears to be acommonality in the fact that growth factors are released whichapplicants find indicative that otherwise dormant cells within thetissue appear to be activated which leads to the remarkable ability ofthe targeted organ or tissue to generate new growth or to regenerateweakened vascular networks in for example the cardio vascular system.This finding leads to a complimentary use of shock wave therapy incombination with stem cell therapies that effectively activate ortrigger stem cells to more rapidly replicate enhancing the ability toharvest and culture more viable cells from the placenta, a nutrientculture of said stem cells, or other sources. The ability to stimulatestem cells can occur within the patients own body activating thenaturally occurring stem cells or stem cells that have been introducedto the patient as part of a treatment beneficially utilizing stem cells.This is a significant clinical value in its own right.

In one embodiment, the invention provides for germicidal cleaning ofbiofilm diseased or infected areas and for wound cleaning generallyafter exposure to surgical procedures.

The use of shock wave therapy requires a fundamental understanding offocused and unfocused shock waves, coupled with a more accuratebiological or molecular model.

Focused shock waves are focused using ellipsoidal reflectors inelectromechanical sources from a cylindrical surface or by the use ofconcave or convex lenses. Piezoelectric sources often use sphericalsurfaces to emit acoustic pressure waves which are self focused and havealso been used in spherical electromagnetic devices.

The biological model proposed by co-inventor Wolfgang Schaden provides awhole array of clinically significant uses of shock wave therapy.

Accepting the biological model as promoted by W. Schaden, the peakpressure and the energy density of the shock waves can be lowereddramatically. Activation of the body's healing mechanisms will be seenby in growth of new blood vessels and the release of growth factors.

The biological model motivated the design of sources with low pressureamplitudes and energy densities. First: spherical waves generatedbetween two tips of an electrode; and second: nearly even wavesgenerated by generalized parabolic reflectors. Third: divergent shockfront characteristics are generated by an ellipsoid behind F2. Unfocusedsources are preferably designed for extended two dimensionalareas/volumes like skin. The unfocused sources can provide a divergentwave pattern a planar or a nearly planar wave pattern and can be used inisolation or in combination with focused wave patterns yielding to animproved therapeutic treatment capability that is non-invasive with fewif any disadvantageous contraindications. Alternatively a focused waveemitting treatment may be used wherein the focal point extendspreferably beyond the target treatment site, potentially external to thepatient. This results in the reduction of or elimination of a localizedintensity zone with associated noticeable pain effect while providing awide or enlarged treatment volume at a variety of depths more closelyassociated with high energy focused wave treatment. The utilization of adiffuser type lens or a shifted far-sighted focal point for theellipsoidal reflector enables the spreading of the wave energy toeffectively create a convergent but off target focal point. This insuresless tissue trauma while insuring cellular stimulation to enhance thehealing process and control the migration or spreading of the infectionwithin the host. More preferably if a resident biofilm location can beisolated and a short, but high energy focused wave pattern can beemitted on the outer barrier of the biofilm causing a fracture orfragmentation in the outer barrier and then a lower unfocused energytransmission can be applied to provide an overall germicidal treatmentand surrounding cell stimulation to destroy the biofilm infected siteand eradicate the resultant microbial debris.

This method of treatment has the steps of, locating a biofilm treatmentsite, region or location, generating either focused, convergent diffusedor far-sighted focused shock waves or unfocused shock waves; directingthese shock waves to the biofilm treatment site; and applying asufficient number of these shock waves to induce an outer barrierbiofilm weakening while simultaneously activating one or more growthfactors in the surrounding tissue cells thereby inducing or acceleratinghealing.

The unfocused shock waves can be of a divergent wave pattern, planar ornear planar pattern preferably convergent diffused or far-sighted wavepattern, of a low peak pressure amplitude and density. Typically theenergy density values range as low as 0.000001 mJ/mm² and having a highend energy density of below 1.0 mJ/mm², preferably 0.20 mJ/mm² or less.The peak pressure amplitude of the positive part of the cycle should beabove 1.0 and its duration is below 1-3 microseconds.

The treatment depth can vary from the surface to the full depth of thetreated organ. The treatment site can be defined by a much largertreatment area than the 0.10-3.0 cm² commonly produced by focused waves.The above methodology is particularly well suited for surface as well assub-surface soft tissue organ treatments.

The above methodology is valuable in generation of tissue,vascularization and may be used in combination with stem cell therapiesas well as regeneration of tissue and vascularization.

The methodology is useful in (re)vascularization and regeneration of theheart, brain, liver, kidney, skin, urological organs, reproductiveorgans, digestive tract and periodontal tissue such as the teeth andgums.

The methodology is useful in stimulating enforcement of defensemechanisms in tissue cells to fight infections from bacteria and can beused germicidally to treat or cleanse wounds or other biofilm targetsites which is a primary concern in the case of treating human diseasessuch as native valve endocarditis, cystic fibrosis, periodontal gumdisease and urinary or digestive tract infections resulting from suchexposures to biofilm type agents.

While the above listed indications cited above are not exhaustive norintended to be limiting, it is exemplary of the wide range of beneficialuses of high energy focused or low energy and amplitude unfocuseddivergent, planar or nearly planar shock waves, convergent shock waves,diffused shock waves or a combination of shock wave types in thetreatment of humans and other mammals that are exposed to a biofilm typeinfection or are at high risk to be so exposed as the result of a highpotential risk to such biofilm infectious exposure.

A most significant method of preventive medicine can be practiced thatis fully enabled by the use of these relatively low amplitude andpressure shock waves. The method includes the steps of identifying highrisk patients for a variety of potential risk conditions. Such conditioncould be by way of example leaking heart valves, urinary infections,degenerative gum disease or cystic fibrosis. After identifying a riskprone candidate providing one or a series of two or more exposuretreatments with focused or unfocused, divergent, planar or near planarshock waves or convergent far-sighted focused shock waves or diffusedshock waves to the treatment site, in this example the regionsurrounding or in proximity to a biofilm occurrence risk location. Thenafter treatments the physician can optionally ultrasound visually orotherwise determine the increase in regeneration or vascularization inthe treated tissue after a period of time. Assuming an initial baselinedetermination of the tissue regeneration or vascularization had beeninitially conducted an estimate or calculation of dosage requirementscan be made. This procedure can be used for any biofilm at riskcondition. After a surgical repair procedure the surrounding tissues canbe post-operatively shock wave treated as well.

The implications of using the (re)generative features of this type ofshock wave therapy are any biofilm weakened organ or tissue even teethor bone can be strengthened to the point of reducing or eliminating therisk of irreparable damage or failure as a result of microbialinfections.

The stimulation of growth factors and activation of healing accelerationwithin the cells of the treated tissues is particularly valuable to hostpatients and other high risk factor subjects wherein conventionalantibiotic treatments have been unsuccessful.

Even more striking as mentioned earlier, early prevention therapies canbe employed to stimulate tissue or organ modeling to be maintainedwithin acceptable ranges prior to an exposure to biofilm infections.This is extremely valuable in the prevention of spreading the infectionfor example. The methods would be to identify at risk patients with aknown biofilm exposure risk, and subjecting that patient to therapeuticshock wave therapy for the purpose of stimulating tissue repair orregeneration effectively remodeling the patient's susceptible organs tobe within accepted functional parameters prior to exposure to a biofilminfection. The objective being to preventively stimulate cellular tissuerepairs to preemptively avoid a degenerative condition from occurringwhich may result in the onset of an antibiotic resistant infection whichcan require invasive surgical procedures.

This preventive therapy is most needed to combat biofilm exposure whichleft untreated results in cellular destruction or any other degenerativeconditions.

FIG. 1 a is a simplified depiction of the a pressure pulse/shock wave(PP/SW) generator, such as a shock wave head, showing focusingcharacteristics of transmitted acoustic pressure pulses. Numeral 1indicates the position of a generalized pressure pulse generator, whichgenerates the pressure pulse and, via a focusing element, focuses itoutside the housing to treat diseases. The affected tissue or organ isgenerally located in or near the focal point which is located in or nearposition 6. At position 17 a water cushion or any other kind of exitwindow for the acoustical energy is located.

FIG. 1 b is a simplified depiction of a pressure pulse/shock wavegenerator, such as a shock wave head, with plane wave characteristics.Numeral 1 indicates the position of a pressure pulse generator accordingto the present invention, which generates a pressure pulse which isleaving the housing at the position 17, which may be a water cushion orany other kind of exit window. Somewhat even (also referred to herein as“disturbed”) wave characteristics can be generated, in case a paraboloidis used as a reflecting element, with a point source (e.g. electrode)that is located in the focal point of the paraboloid. The waves will betransmitted into the patient's body via a coupling media such as, e.g.,ultrasound gel or oil and their amplitudes will be attenuated withincreasing distance from the exit window 17.

FIG. 1 c is a simplified depiction of a pressure pulse shock wavegenerator (shock wave head) with divergent wave characteristics. Thedivergent wave fronts may be leaving the exit window 17 at point 11where the amplitude of the wave front is very high. This point 17 couldbe regarded as the source point for the pressure pulses. In FIG. 1 c thepressure pulse source may be a point source, that is, the pressure pulsemay be generated by an electrical discharge of an electrode under waterbetween electrode tips. However, the pressure pulse may also begenerated, for example, by an explosion, referred to as a ballisticpressure pulse. The divergent characteristics of the wave front may be aconsequence of the mechanical setup shown in FIG. 2 b.

FIG. 2 a is a simplified depiction of a pressure pulse/shock wavegenerator (shock wave head) according to the present invention having anadjustable or exchangeable (collectively referred to herein as“movable”) housing around the pressure wave path. The apparatus is shownin a focusing position. FIG. 2 a is similar to FIG. 1 a but depicts anouter housing (16) in which the acoustical pathway (pressure wave path)is located. In a preferred embodiment, this pathway is defined byespecially treated water (for example, temperature controlled,conductivity and gas content adjusted water) and is within a watercushion or within a housing having a permeable membrane, which isacoustically favorable for the transmission of the acoustical pulses. Incertain embodiments, a complete outer housing (16) around the pressurepulse/shock wave generator (1) may be adjusted by moving this housing(16) in relation to, e.g., the focusing element in the generator.However, as the person skilled in the art will appreciate, this is onlyone of many embodiments of the present invention. While the figure showsthat the exit window (17) may be adjusted by a movement of the completehousing (16) relative to the focusing element, it is clear that asimilar, if not the same, effect can be achieved by only moving the exitwindow, or, in the case of a water cushion, by filling more water in thevolume between the focusing element and the cushion. FIG. 2 a shows thesituation in which the arrangement transmits focused pressure pulses.

FIG. 2 b is a simplified depiction of the pressure pulse/shock wavegenerator (shock wave head) having an adjustable or exchangeable housingaround the pressure wave path with the exit window 17 being in thehighest energy divergent position. The configuration shown in FIG. 2 bcan, for example, be generated by moving the housing (16) including theexit window (17), or only the exit window (17) of a water cushion,towards the right (as shown in the Figure) to the second focus f2 (20)of the acoustic waves. In a preferred embodiment, the energy at the exitwindow will be maximal. Behind the focal point, the waves may be movingwith divergent characteristics (21).

FIG. 2 c is a simplified depiction of the pressure pulse/shock wavegenerator (shock wave head) having an adjustable or exchangeable housingaround the pressure wave path in a low energy divergent position. Theadjustable housing or water cushion is moved or expanded much beyond f2position (20) so that highly divergent wave fronts with low energydensity values are leaving the exit window (17) and may be coupled to apatient's body. Thus, an appropriate adjustment can change the energydensity of a wave front without changing its characteristic.

This apparatus may, in certain embodiments, be adjusted/modified/or thecomplete shock wave head or part of it may be exchanged so that thedesired and/or optimal acoustic profile such as one having wave frontswith focused, planar, nearly plane, convergent or divergentcharacteristics can be chosen.

A change of the wave front characteristics may, for example, be achievedby changing the distance of the exit acoustic window relative to thereflector, by changing the reflector geometry, by introducing certainlenses or by removing elements such as lenses that modify the wavesproduced by a pressure pulse/shock wave generating element. Exemplarypressure pulse/shock wave sources that can, for example, be exchangedfor each other to allow an apparatus to generate waves having differentwave front characteristics are described in detail below.

In certain embodiments, the change of the distance of the exit acousticwindow can be accomplished by a sliding movement. However, in otherembodiments of the present invention, in particular, if mechanicalcomplex arrangements, the movement can be an exchange of mechanicalelements.

In one embodiment, mechanical elements that are exchanged to achieve achange in wave front characteristics include the primary pressure pulsegenerating element, the focusing element, the reflecting element, thehousing and the membrane. In another embodiment, the mechanical elementsfurther include a closed fluid volume within the housing in which thepressure pulse is formed and transmitted through the exit window.

In one embodiment, the apparatus of the present invention is used incombination therapy. Here, the characteristics of waves emitted by theapparatus are switched from, for example, focused to divergent or fromdivergent with lower energy density to divergent with higher energydensity. Thus, effects of a pressure pulse treatment can be optimized byusing waves having different characteristics and/or energy densities,respectively.

While the above described universal toolbox of the present inventionprovides versatility, the person skilled in the art will appreciate thatapparatuses that only produce waves having, for example, nearly planecharacteristics, are less mechanically demanding and fulfill therequirements of many users.

As the person skilled in the art will also appreciate that embodimentsshown in the drawings are independent of the generation principle andthus are valid for not only electro-hydraulic shock wave generation butalso for, but not limited to, PP/SW generation based on electromagnetic,piezoceramic and ballistic principles. The pressure pulse generatorsmay, in certain embodiments, be equipped with a water cushion thathouses water which defines the path of pressure pulse waves that is,through which those waves are transmitted. In a preferred embodiment, apatient is coupled via ultrasound gel or oil to the acoustic exit window(17), which can, for example, be an acoustic transparent membrane, awater cushion, a plastic plate or a metal plate.

FIG. 3 is a simplified depiction of the pressure pulse/shock waveapparatus having no focusing reflector or other focusing element. Thegenerated waves emanate from the apparatus without coming into contactwith any focusing elements. FIG. 3 shows, as an example, an electrode asa pressure pulse generating element producing divergent waves (28)behind the ignition point defined by a spark between the tips of theelectrode (23, 24).

FIG. 4 a is a simplified depiction of the pressure pulse/shock wavegenerator (shock wave head) having as focusing element an ellipsoid(30). Thus, the generated waves are focused at (6).

FIG. 4 b is a simplified depiction of the pressure pulse/shock wavegenerator (shock wave head) having as a focusing element an paraboloid(y²=2px). Thus, the characteristics of the wave fronts generated behindthe exit window (33, 34, 35, and 36) are disturbed plane (“parallel”),the disturbance resulting from phenomena ranging from electrode burndown, spark ignition spatial variation to diffraction effects. However,other phenomena might contribute to the disturbance.

FIG. 4 c is a simplified depiction of the pressure pulse/shock wavegenerator (shock wave head) having as a focusing element a generalizedparaboloid (y^(n)=2px, with 1.2<n<2.8 and n≠2). Thus, thecharacteristics of the wave fronts generated behind the exit window (37,38, 39, and 40) are, compared to the wave fronts generated by aparaboloid (y²=2px), less disturbed, that is, nearly plane (or nearlyparallel or nearly even (37, 38, 39, 40)). Thus, conformationaladjustments of a regular paraboloid (y²=2px) to produce a generalizedparaboloid can compensate for disturbances from, e.g., electrode burndown. Thus, in a generalized paraboloid, the characteristics of the wavefront may be nearly plane due to its ability to compensate for phenomenaincluding, but not limited to, burn down of the tips of the electrodeand/or for disturbances caused by diffraction at the aperture of theparaboloid. For example, in a regular paraboloid (y²=2px) with p=1.25,introduction of a new electrode may result in p being about 1.05. If anelectrode is used that adjusts itself to maintain the distance betweenthe electrode tips (“adjustable electrode”) and assuming that theelectrodes burn down is 4 mm (z=4 mm), p will increase to about 1.45. Tocompensate for this burn down, and here the change of p, and to generatenearly plane wave fronts over the life span of an electrode, ageneralized paraboloid having, for example n=1.66 or n=2.5 may be used.An adjustable electrode is, for example, disclosed in U.S. Pat. No.6,217,531.

FIG. 4 d shows sectional views of a number of paraboloids. Numeral 62indicates a paraboloid of the shape y²=2px with p=0.9 as indicated bynumeral 64 at the x axis which specifies the p/2 value (focal point ofthe paraboloid). Two electrode tips of a new electrode 66 (inner tip)and 67 (outer tip) are also shown in the Figure. If the electrodes arefired and the tips are burning down the position of the tips change, forexample, to position 68 and 69 when using an electrode which adjusts itsposition to compensate for the tip burn down. In order to generatepressure pulse/shock waves having nearly plane characteristics, theparaboloid has to be corrected in its p value. The p value for theburned down electrode is indicate by 65 as p/2=1. This value, whichconstitutes a slight exaggeration, was chosen to allow for an easierinterpretation of the Figure. The corresponding paraboloid has the shapeindicated by 61, which is wider than paraboloid 62 because the value ofp is increased. An average paraboloid is indicated by numeral 60 inwhich p=1.25 cm. A generalized paraboloid is indicated by dashed line 63and constitutes a paraboloid having a shape between paraboloids 61 and62. This particular generalized paraboloid was generated by choosing avalue of n≠2 and a p value of about 1.55 cm. The generalized paraboloidcompensates for different p values that result from the electrode burndown and/or adjustment of the electrode tips.

FIG. 5 is a simplified depiction of a set-up of the pressure pulse/shockwave generator (43) (shock wave head) and a control and power supplyunit (41) for the shock wave head (43) connected via electrical cables(42) which may also include water hoses that can be used in the contextof the present invention. However, as the person skilled in the art willappreciate, other set-ups are possible and within the scope of thepresent invention.

FIG. 6 is a simplified depiction of the pressure pulse/shock wavegenerator (shock wave head) having an electromagnetic flat coil 50 asthe generating element. Because of the plane surface of the acceleratedmetal membrane of this pressure pulse/shock wave generating element, itemits nearly plane waves which are indicated by lines 51. In shock waveheads, an acoustic lens 52 is generally used to focus these waves. Theshape of the lens might vary according to the sound velocity of thematerial it is made of. At the exit window 17 the focused waves emanatefrom the housing and converge towards focal point 6.

FIG. 7 is a simplified depiction of the pressure pulse/shock wavegenerator (shock wave head) having an electromagnetic flat coil 50 asthe generating element. Because of the plane surface of the acceleratedmetal membrane of this generating element, it emits nearly plane waveswhich are indicated by lines 51. No focusing lens or reflecting lens isused to modify the characteristics of the wave fronts of these waves,thus nearly plane waves having nearly plane characteristics are leavingthe housing at exit window 17.

FIG. 8 is a simplified depiction of the pressure pulse/shock wavegenerator (shock wave head) having an piezoceramic flat surface withpiezo crystals 55 as the generating element. Because of the planesurface of this generating element, it emits nearly plane waves whichare indicated by lines 51. No focusing lens or reflecting lens is usedto modify the characteristics of the wave fronts of these waves, thusnearly plane waves are leaving the housing at exit window 17. Emittingsurfaces having other shapes might be used, in particular curvedemitting surfaces such as those shown in FIGS. 4 a to 4 c as well asspherical surfaces. To generate waves having nearly plane or divergentcharacteristics, additional reflecting elements or lenses might be used.The crystals might, alternatively, be stimulated via an electroniccontrol circuit at different times, so that waves having plane ordivergent wave characteristics can be formed even without additionalreflecting elements or lenses.

FIG. 9 is a simplified depiction of the pressure pulse/shock wavegenerator (shock wave head) comprising a cylindrical electromagnet as agenerating element 53 and a first reflector having a triangular shape togenerate nearly plane waves 54 and 51. Other shapes of the reflector oradditional lenses might be used to generate divergent waves as well.

With reference to FIGS. 10, 11 and 12 a schematic view of a shock wavegenerator or source 1 is shown emitting a shock wave front 200 from anexit window 17. The shock wave front 200 has converging waves 202extending to a focal point or focal geometric volume 20 at a locationspaced a distance X from the generator or source 1. Thereafter the wavefront 200 passes from the focal point or geometric volume 20 in adiverging wave pattern as has been discussed in the various other FIGS.1-9 generally.

With particular reference to FIG. 10 an organ 100 is shown generallycentered on the focal point or volume 20 at a location X₀ within theorgan 100. In this orientation the emitted waves are focused and thusare emitting a high intensity acoustic energy at the location X₀. Thislocation X₀ can be anywhere within or on the organ. Assuming the organ100 is a tissue having a biofilm mass 102 at location X₀ then the focusis located directly on the biofilm mass 102. In one method of treating abiofilm infection or mass 102 these focused waves can be directed todestroy or otherwise reduce the biofilm mass 102 by weakening the outerbarrier shield of the biofilm mass 102.

With reference to FIG. 11, the organ 100 is shifted a distance X towardthe generator or source 1. The organ 100 at location X₀ being positioneda distance X-X₁ from the source 1. This insures the organ 100 isimpinged by converging waves 202 but removed from the focal point 20.When the organ 100 is tissue this bombardment of converging waves 202stimulates the cells activating the desired healing response aspreviously discussed.

With reference to FIG. 12, the organ 100 is shown shifted or located inthe diverging wave portion 204 of the wave front 200. As shown X₀ is nowat a distance X₂ from the focal point or geometric volume 20 located ata distance X from the source 1. Accordingly X₀ is located a distanceX+X₂ from the source 1. As in FIG. 10 this region of diverging waves 204can be used to stimulate the organ 100 which when the organ is acellular tissue stimulates the cells to produce the desired healingeffect or response.

Heretofore invasive techniques were not used in combination with shockwave therapy primarily because the shock waves were believed to be ableto sufficiently pass through interfering body tissue to achieve thedesired result in a non-invasive fashion. While this may be true, inmany cases if the degenerative process is such that an operation isrequired then the combination of an operation in conjunction with shockwave therapy only enhances the therapeutic values and the healingprocess of the patient and the infected organ such that regenerativeconditions can be achieved that would include not only revascularizationof the heart or other organs wherein sufficient or insufficient bloodflow is occurring but also to enhance the improvement of ischemic tissuethat may be occupying a portion of the infected tissue or organ. Thisischemic tissue can then be minimized by the regenerative process ofusing shock wave therapy in the fashion described above to permit thetissue to rebuild itself in the region that has been afflicted.

As shown in FIGS. 1-12 the use of these various acoustic shock waveforms can be used separately or in combination to achieve the desiredtherapeutic effect of destroying the biofilm mass 102.

Furthermore such acoustic shock wave forms can be used in combinationwith drugs, chemical treatments, irradiation therapy or even physicaltherapy and when so combined the stimulated cells will more rapidlyassist the body's natural healing response.

The present invention provides an apparatus for an effective treatmentof indications, which benefit from high or low energy pressurepulse/shock waves having focused or unfocused, nearly plane, convergentor even divergent characteristics. With an unfocused wave having nearlyplane, plane, convergent wave characteristic or even divergent wavecharacteristics, the energy density of the wave may be or may beadjusted to be so low that side effects including pain are very minor oreven do not exist at all.

In certain embodiments, the apparatus of the present invention is ableto produce waves having energy density values that are below 0.1 mJ/mm2or even as low as 0.000 001 mJ/mm2. In a preferred embodiment, those lowend values range between 0.1-0.001 mJ/mm2. With these low energydensities, side effects are reduced and the dose application is muchmore uniform. Additionally, the possibility of harming surface tissue isreduced when using an apparatus of the present invention that generatesunfocused waves having planar, nearly plane, convergent or divergentcharacteristics and larger transmission areas compared to apparatusesusing a focused shock wave source that need to be moved around to coverthe affected area. The apparatus of the present invention also may allowthe user to make more precise energy density adjustments than anapparatus generating only focused shock waves, which is generallylimited in terms of lowering the energy output. Nevertheless in somecases the first use of a high energy focused shock wave targeting thebiomass may be the best approach to weaken the outer barrier of theshield of the biomass followed by a transmission of lower energyunfocused wave patterns, the combination being the most effective ingermicidal destruction of the biofilm mass.

The treatment of the above mentioned tissue, organ or body of a patientis believed to be a first time use of acoustic shock wave therapy in thepreventive pre-exposure or post-exposure to biofilm infections. None ofthe work done to date has treated the above mentioned biofilm infectionswith convergent, divergent, planar or near-planar acoustic unfocusedshock waves of low energy or high energy focused shock waves in agermicidal transmission path from the emitting source lens or cover tothe infection. Also this is believed to be a first time use of acousticshock waves for germicidal wound cleaning or preventive medicaltreatments for such exposures.

It will be appreciated that the apparatuses and processes of the presentinvention can have a variety of embodiments, only a few of which aredisclosed herein. It will be apparent to the artisan that otherembodiments exist and do not depart from the spirit of the invention.Thus, the described embodiments are illustrative and should not beconstrued as restrictive.

The use of acoustic shock waves to patients exposed to biofilminfections stimulates a cellular response of the treated tissues as wellas a cellular response in the surrounding tissue. This responseactivates otherwise dormant cells to increase the body's own defensemechanisms, allowing the cells to limit the migration of the infectionand resultant tissue damage, but also to initiate the healing process.This feature means that the treating physician has the added benefit ofa patient whose body will be strengthened to mitigate damage tootherwise healthy tissues and organs.

The nature of infectious disease treatments employing only antibioticsto kill infections is well known to actually make biofilm protectedmicroorganisms mutate making them even harder to kill. The result is thepatient is in a greatly weakened state overall. These mutant strains areso severe that the common antibiotic treatments are losing their abilityto stop the spread of some infections which is well documented. Thesesymptoms are generally reversible. The more serious complications maynot be reversible. In some cases gum damage and complete destruction ofthe teeth has been observed as a consequence of such failed treatments.These antibiotic treatments can be cumulative in their adverse reactionsand thus the effective treatment of the infections can also permanentlydamage otherwise healthy tissue and organs. The use of the shock wavesas described above stimulates these healthy cells to defend against thisspill over intrusion.

This means the physician can use these antibiotic treatments with farless adverse reactions if he combines the treatments with one or moreexposures to acoustic shock waves either before introducing chemicalantibiotic agents or shortly thereafter or both. This further means thatthe patient's recovery time should be greatly reduced because thepatient treated with shock waves will have initiated a healing responsethat is much more aggressive than heretofore achieved without thecellular stimulation provided by pressure pulse or shock wavetreatments. The current use of medications to stimulate such cellularactivity is limited to absorption through the bloodstream via the bloodvessels. Acoustic shock waves stimulate all the cells in the regiontreated activating an almost immediate cellular release of infectionfighting and healing agents. Furthermore, as the use of other wiseconflicting chemicals is avoided, adverse side effects can be limited tothose medicaments used to destroy the infectious cells. In other wordsthe present invention is far more complimentary to such antibiotictreatments in that the stimulation of otherwise healthy cells willgreatly limit the adverse and irreversible effects on the surroundingnon-infected tissues and organs.

A further benefit of the use of acoustic shock waves is there are noknown adverse indications when combined with the use of othermedications or drugs. In fact the activation of the cells exposed toshock wave treatments only enhances cellular absorption of suchmedication making these drugs faster acting than when compared to nonstimulated cells. As a result, it is envisioned that the use of one ormore medicaments prior to, during or after subjecting the patient toacoustic shock waves will be complimentary to the treatment orpre-conditioning treatment for biofilm exposures. It is furtherappreciated that certain drug therapies can be altered or modified tolower risk or adverse side effects when combined with a treatmentinvolving acoustic shock waves as described above.

In the case wherein the patient is a victim of a biofilm as the resultof a biological accident or a biological attack, the immediate use ofshock waves shortly after exposure can be an effective tool in savinglives. The body's ability to recover is enhanced and the damaged tissuecan be more quickly replaced by stimulated healthy cells which is aregenerative feature of the use of shock wave treatments.

This is particularly true in the case of infections of the skin causedby biological agents. The wounded tissue is a source of rapidlyspreading infection which can lead to a complete failure of the bodyleading to death. The use of shock wave treatments is a valuable tool insuch a case because acoustic shock waves can be provided on a virtuallylimitless basis as long as connected to an adequate power source.Normally supplies of medicines are limited and almost never near thearea most in need. Accordingly vehicles similar to emergency trucks usedto transport patients can be equipped with shock wave generators so thatin field treatments can be conducted on a wide scale quickly. This alonecould greatly reduce the loss of life that would occur by delays intreatment.

Variations in the present invention are possible in light of thedescription of it provided herein. While certain representativeembodiments and details have been shown for the purpose of illustratingthe subject invention, it will be apparent to those skilled in this artthat various changes and modifications can be made therein withoutdeparting from the scope of the subject invention. It is, therefore, tobe understood that changes can be made in the particular embodimentsdescribed which will be within the full intended scope of the inventionas defined by the following appended claims.

1. The method of treating a host diagnosed with one or more biofilms,the biofilms having an outer barrier and an underlying colony oforganisms comprises the steps of: receiving a host diagnosed with one ormore biofilms; locating a region or location of a resident biofilm;activating a pressure pulse or acoustic shock wave generating source,the pressure pulse being an acoustic pulse which includes several cyclesof positive and negative pressure, wherein the pressure pulse has anamplitude of the positive part of such a cycle should be above 0.1 MPaand the time duration of the pressure pulse is from below a microsecondto about a second, rise times of the positive part of the first pressurecycle in the range of nano-seconds (ns) up to some milli-seconds (ms),the acoustic shock waves being very fast pressure pulses havingamplitudes above 0.1 MPa and rise times of the amplitude being below100's of ns, the duration of the shock wave is typically below 1-3micro-seconds (μs) for the positive part of a cycle and typically abovesome micro-seconds for the negative part of a cycle; emitting pressurepulses or acoustic shock waves using focused pulses or shock waves at anenergy density up to 1.0 mmJ/mm²; with or without creating cavitationbubbles in the location or region of the resident biofilm, the focusedpulses or shock waves having a focal volume or point on the location orregion of the resident biofilm or using unfocused pulses or shock wavesand away from any localized geometric focal volume or point of theemitted shock waves wherein the emitted shock waves or pressure pulseseither have no geometric focal volume or point or have a focal volume orpoint ahead of the location or region of a resident biofilm or beyondthe location or region of a resident biofilm thereby passing the emittedwaves or pulses through the location or region of a resident biofilmwhile avoiding having any localized focal point within the location orregion of a resident biofilm wherein the emitted pressure pulses orshock waves are convergent, divergent, planar or near planar and thepressure pulse shock wave generator or source is based onelectro-hydraulic, electromagnetic, piezoceramic or ballistic wavegeneration having an energy density value ranging as low as 0.00001mJ/mm² to a high end of below 1.0 mJ/mm²; and directing the pulses orshock waves to impinge the resident biofilm to destroy, fracture,fragment or otherwise open the outer barrier structure of the residentbiofilm.
 2. The method of claim 1 further comprises the step of:stimulating cells of a host to initiate a cellular response within thehost when the host is a living being with organs and tissues having acellular structure, the stimulated cells assist in absorbing orotherwise eradicating the biofilm.
 3. The method of claim 1 wherein theemitted pressure pulses or shock waves impinge the underlying organismsdestroying or rupturing their outer membranes to germicidally kill theorganisms.
 4. The method of claim 1 further comprises the step of:administering one or more drugs, antibiotics or other medication to thehost.
 5. The method of claim 1 further comprises the step of: surgicallyexposing the region or location of the resident biofilm.
 6. The methodof treatment of claim 1 wherein the emitted shock waves are convergent,divergent, planar or near planar.
 7. The method of treatment of claim 1wherein the emitted pressure pulses or shock waves are convergent havingone or more geometric focal volumes of points at a distance of at leastX from the generator or source, the method further comprisingpositioning the organ at a distance at or less than the distance X fromthe source.
 8. The method of treatment of claim 1 further comprises thestep of: administering one or more medicaments prior, during or aftersubjecting the patient to pressure pulses or acoustic shock waves. 9.The method of treatment of claim 1 further comprises the step of:subjecting a tissue or organ to a surgical procedure to remove some orall of a biofilm growth.
 10. The method of claim 1 wherein the region orlocation is part of a system including the cardiovascular, urological,reproductive, digestive, intestinal, neurological or periodontal. 11.The method of claim 1 wherein the pathological or degenerative conditionis a leaking valve in a heart.
 12. The method of claim 1 wherein thepathological condition is a degenerative gum condition.
 13. The methodof claim 1 wherein the pathological condition is an infection.
 14. Themethod of claim 1 wherein the infection is generally non-responsive tomedications.
 15. The method of preventively treating a patient at riskof developing a biofilm and becoming a host; comprises the steps of:identifying an at risk patient with a pathological or degenerativecondition susceptible to the generation of a biofilm; treating the atrisk patient by: locating the location or region to be treated;activating a pressure pulse or acoustic shock wave generating source,the pressure pulse being an acoustic pulse which includes several cyclesof positive and negative pressure, wherein the pressure pulse has anamplitude of the positive part of such a cycle should be above 0.1 MPaand the time duration of the pressure pulse is from below a microsecondto about a second, rise times of the positive part of the first pressurecycle in the range of nano-seconds (ns) up to some milli-seconds (ms),the acoustic shock waves being very fast pressure pulses havingamplitudes above 0.1 MPa and rise times of the amplitude being below100's of ns, the duration of the shock wave is typically below 1-3micro-seconds (μs) for the positive part of a cycle and typically abovesome micro-seconds for the negative part of a cycle; and emittingpressure pulses or acoustic shock waves using focused or unfocusedpulses or shock waves at an energy density up to 1.0 mmJ/mm² anddirecting the pulses or shock waves to impinge an area of the treatmentregion or location; in the absence of a focal point impinging thetreatment region or location to stimulate a cellular response in theabsence of creating cavitation bubbles in the location or regionevidenced by not experiencing the sensation of hemorrhaging caused bythe emitted waves or pulses wherein the area of the treatment region orlocation is away from any localized geometric focal volume or point ofthe emitted shock waves wherein the emitted shock waves or pressurepulses either have no geometric focal volume or point or have a focalvolume or point ahead of the location or region of treatment or beyondthe location or region of treatment thereby passing the emitted waves orpulses through the location or region of treatment while avoiding havingany localized focal point within the location or region of treatmentwherein the emitted pressure pulses or shock waves are convergent,divergent, planar or near planar and the pressure pulse shock wavegenerator or source is based on electro-hydraulic, electromagnetic,piezoceramic or ballistic wave generation having an energy density valueranging as low as 0.00001 mJ/mm² to a high end of below 1.0 mJ/mm². 16.The method of claim 15 wherein the region or location is part of asystem including the cardiovascular, urological, reproductive,digestive, intestinal, neurological or periodontal tissue.
 17. Themethod of claim 15 wherein the pathological or degenerative condition isa leaking valve in a heart.
 18. The method of claim 15 wherein thepathological condition is a degenerative gum condition.
 19. The methodof claim 15 wherein the pathological condition is an infection.
 20. Themethod of claim 19 wherein the infection is generally non-responsive tomedications.